Application of β-Phosphorylated Nitroethenes in [3+2] Cycloaddition Reactions Involving Benzonitrile N-Oxide in the Light of a DFT Computational Study

Karolina Zawadzińska,Karolina Kula

doi:10.3390/org2010003

Abstract

The regiochemistry of [3+2] cycloaddition (32CA) processes between benzonitrile N-oxide 1 and β-phosphorylated analogues of nitroethenes 2a–c has been studied using the Density Functional Theory (DFT) at the M062X/6-31+G(d) theory level. The obtained results of reactivity indices show that benzonitrile N-oxide 1 can be classified both as a moderate electrophile and moderate nucleophile, while β-phosphorylated analogues of nitroethenes 2a–c can be classified as strong electrophiles and marginal nucleophiles. Moreover, the analysis of CDFT shows that for [3+2] cycloadditions with the participation of β-phosphorylatednitroethene 2a and β-phosphorylated α-cyanonitroethene 2b, the more favored reaction path forms 4-nitro-substituted Δ2-isoxazolines 3a–b, while for a reaction with β-phosphorylated β-cyanonitroethene 2c, the more favored path forms 5-nitro-substituted Δ2-isoxazoline 4c. This is due to the presence of a cyano group in the alkene. The CDFT study correlates well with the analysis of the kinetic description of the considered reaction channels. Moreover, DFT calculations have proven the clearly polar nature of all analyzed [3+2] cycloaddition reactions according to the polar one-step mechanism.

Highlights

The [3+2] cycloadditions (32CA) are all-purpose strategiesto the regio- and stereoselective synthesis of five-membered heterocyclic molecular systems [1,2,3,4]
Our theoretical study was divided into three parts: (i) firstly, the analysis of the electronic properties of addends and their intermolecular interactions according to Conceptual Density Functional Theory (CDFT) reactivity indices was carried out; (ii) in the paragraph, reaction profiles of [3+2] cycloaddition between benzonitrile N-oxide 1 and β-phosphorylated analogues of nitroethenes 2a–c are explored and characterized; (iii) at the end, a full diagnostic of all critical structures of reaction 1 with 2a–c are studied
The reactions of [3+2] cycloaddition between benzonitrile N-oxide 1 and β-phosphory lated analogues of nitroethenes 2a–c have been studied according to M062X/6-31+G(d) theory level

Summary

Introduction

The [3+2] cycloadditions (32CA) are all-purpose strategiesto the regio- and stereoselective synthesis of five-membered heterocyclic molecular systems [1,2,3,4] These types of reactions generally proceed under mild conditions, without the presence of catalysts, giving high yields of target compounds [2,3,4]. Reactions between nitrile N-oxides and alkenes obtain ∆2 -isoxazolines, which are widely spread out as biological and pharmacological substances. They exhibit, for example, an antibacterial [11] and an antiviral [12]. The possibility of attaching both of these groups in a one-step process provides the 32CA reactions between nitrile N-oxide and phosphorylated analogues of nitroethene. We hope that our study will provide a better understanding of intermolecular interactions of addends and the probable selectivity and the mechanism created by these heterocyclic organic compounds, especially for synthetic chemists

Computational Details

Results and Discussion

Conclusions